Long-Term Outcomes in Patients With Diabetes Mellitus Related to Prolonging Clopidogrel More Than 12 Months After Coronary Stenting

J Am Coll Cardiol. 2015 Sep 8;66(10):1091-101. doi: 10.1016/j.jacc.2015.06.1339.

Abstract

Background: Recent large clinical trials show lower rates of late cardiovascular events by extending clopidogrel >12 months after percutaneous coronary revascularization (PCI). However, concerns of increased bleeding have elicited support for limiting prolonged treatment to high-risk patients.

Objectives: The aim of this analysis was to determine the effect of prolonging clopidogrel therapy >12 months versus ≤12 months after PCI on very late outcomes in patients with diabetes mellitus (DM).

Methods: Using the Veterans Health Administration, 28,849 patients undergoing PCI between 2002 and 2006 were categorized into 3 groups: 1) 16,332 without DM; 2) 9,905 with DM treated with oral medications or diet; and 3) 2,612 with DM treated with insulin. Clinical outcomes, stratified by stent type, ≤4 years after PCI were determined from the Veterans Health Administration and Medicare databases and risk was assessed by multivariable and propensity score analyses using a landmark analysis starting 1 year after the index PCI. The primary endpoint of the study was the risk of all-cause death or myocardial infarction (MI).

Results: In patients with DM treated with insulin who received drug-eluting stents (DES), prolonged clopidogrel treatment was associated with a decreased risk of death (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.42 to 0.82) and death or MI (HR: 0.67; 95% CI: 0.49 to 0.92). Similarly, in patients with noninsulin-treated DM receiving DES, prolonged clopidogrel treatment was associated with less death (HR: 0.61; 95% CI: 0.48 to 0.77) and death or MI (HR: 0.61; 95% CI: 0.5 to 0.75). Prolonged clopidogrel treatment was not associated with a lower risk in patients without DM or in any group receiving bare-metal stents.

Conclusions: Extending the duration of clopidogrel treatment >12 months may decrease very late death or MI only in patients with DM receiving first-generation DES. Future studies should address this question in patients receiving second-generation DES.

Keywords: clopidogrel; diabetes mellitus; long-term outcomes; percutaneous coronary interventions.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Analysis of Variance
  • Angioplasty, Balloon, Coronary / methods*
  • Angioplasty, Balloon, Coronary / mortality
  • Cause of Death*
  • Clopidogrel
  • Cohort Studies
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / mortality*
  • Coronary Artery Disease / therapy*
  • Databases, Factual
  • Diabetes Mellitus / diagnosis
  • Diabetes Mellitus / mortality*
  • Diabetes Mellitus / therapy
  • Drug Administration Schedule
  • Drug-Eluting Stents
  • Female
  • Follow-Up Studies
  • Humans
  • Insulin / administration & dosage
  • Long-Term Care
  • Male
  • Medicare / statistics & numerical data
  • Middle Aged
  • Multivariate Analysis
  • Platelet Aggregation Inhibitors / administration & dosage
  • Postoperative Care / methods
  • Propensity Score
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Assessment
  • Severity of Illness Index
  • Survival Rate
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Time Factors
  • Treatment Outcome
  • United States
  • Veterans Disability Claims / statistics & numerical data

Substances

  • Insulin
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine